CS268281B1 - 2,4-Dioxo-4- (4-pentyloxyphenyl) butanoic acid esters - Google Patents

Abstract

The speech refers to esters of 2,4-dioxo-4-(4-pentyloxy-phenyl)butanoic acid of the general formula I C5H110-(CgH5)-COCH2COCOOR (I), where R is a methyl or ethyl group. These new yet undescribed substances show anthelmintic activity against the model helminth Hymenolepis nana.

Description

The invention relates to 2,4-dioxo-4- (4-pentyloxyphenyl) butanoic acid esters of the general formula I ^C 5 ^H 11 °

COCH ₂ COCOOR (I).

wherein R is methyl or ethyl.

These new previously undescribed substances show useful anthelmintic activity, especially against the model helminth Hymenolepis nana.

The compounds of formula I can be prepared according to the invention by reacting 4-pentyloxyaoetophenone and an equivalent amount of dimethyl oxalate or diethyl oxalate or sodium methanolate or ethanolate at 20 ° C.

Evaluation of anthelmintic efficacy against the model helminth Hymenolepis nana:

The tests were performed on male mice of strain H weighing 10 to 13 g in groups of 6. Two of the three control groups were invaded, untreated, the third invaded, treated with a standard preparation - the piperazine salt of niclosamide - against which the efficacy of the substances was compared.

Invasion was performed by gavage orally of 500 mature Hymenolepis nana eggs in a volume of 0.25 ml / mouse. The compounds of formula I were administered orally 13 days and 14 days after invasion by gavage at a dose of 150 mg.kg ^-1 body weight (wt.) As a homogenate in Dorfman's reagent. Mice were sacrificed 3 days after application, and after determining the total number of tasemnio with scolexes in a complete helmintological autopsy of the small intestine of mice, the anthelmintic efficacy was determined by calculation by the Steward indirect activity method. The standard was also applied 13 and 14 days after invasion at a dose of 150 mg.kg ^-1 . wt., which, calculated on niclosamide, means a dose of 4.48.10 "^ mol.kg" ¹ b. hm.

The anthelmintic activity of the compounds of formula I against the model helminth Hymenolepis nana expressed as a percentage by the Steward indirect activity method is shown below.

substance according to dose example moth. kg " design of. hm. 1 5,13.10 " 2 4,89.10 "

efficiency in% by the method of indirect activity

The process for the preparation of the substances according to the invention is simple and provides the desired products in satisfactory yields. Further details follow from the following examples, which merely illustrate the invention and do not limit it.

Example 1

2,4-Dioxo-4- (4-pentyloxyphenyl) butanoic acid methyl ester

a) To a solution of sodium methanolate prepared by dissolving 7.7 g (0.33 mol) of sodium in 290 methanol at 67 ° C were added 67 g (0.33 mol) of 4-pentyloxyacetophenone and 39 g (0.33 mol) of dimethyl oxalate and the reaction mixture is filtered off with suction after stirring for 4 hours.

The aspirated substance was triturated and then shaken in a mixture of 400 ml of water with 50 ml of 1 M sulfuric acid and 700 ml of diethyl ether. The aqueous portion was repeatedly shaken with diethyl ether and the combined ether portions were dried to dryness over anhydrous sodium sulfate. 45 * 6 g (48%) of the substance * are obtained after crystallization from ethanol melting at 62 DEG C., which has a composition of .alpha.

b) A solution of 30.9 g (0.15 mol) of 4-pentyloxyacetophenone and 21.9 g of (0.15 mol) of diethyl oxalate in 40 ml of methanol. After stirring for 4 hours at 20 [deg.] C., the precipitate was filtered off with suction and triturated dry. It was then triturated with a mixture of 290 ml of water and 28 ml of 1 M sulfuric acid and 400 ml of diethyl ether. The aqueous layer was shaken repeatedly with diethyl ether and the combined ethers were dried to dryness over anhydrous sodium sulfate. 33.2 g (76%) of material with a melting point of 60.5-62.3 DEG C. are obtained. After crystallization from ethanol, the m.p. and composition of the substance were the same as for the product prepared according to Example 1a).

Example 2

2,4-Dioxo-4- (4-pentyloxyphenyl) butanoic acid ethyl ester

To a solution of sodium ethanolate prepared from 3.5 g (0.15 mol) of sodium and 200 ml of ethanol at 20 ° C were added 30.9 g (0.15 mol) of 4-pentyloxyacetophenone and 21.9 g (0.15 mol) of mol) of diethyl oxalate and the reaction mixture is filtered off with suction after stirring for 4 hours. The aspirated substance was triturated and then shaken in a mixture of 300 ml of water with 40 ml of 1 M sulfuric acid and 1500 ml of diethyl ether. The aqueous portion was shaken repeatedly with diethyl ether and the combined ether portions were dried to dryness over anhydrous sodium sulfate. 24.7 g (54%) of material are obtained, after crystallization from hexane, melting at 44 DEG-45 DEG C., which has a composition of C _{@ 1} H2 O 2 C and a mass spectrum of m / z 306 (M @ +).

Claims (1)

OBJECT OF THE INVENTION 2,4-Dioxo-4- (4-pentyloxyphenyl) butanoic acid esters of formula I ^C 5 ^H 11 ° C0CH ₂ C0C00R (I). wherein R is methyl or ethyl.